DIMENSIONS Winter 2002

Spotlight on Research: Ten-year Kame project yields clues to how lifestyle affects aging and the development of AD

by Cheryl Dawes

Each morning our senses awaken to the sights, sounds and smells that make up our environment. The environment in which we live encompasses our culture, language and lifestyle. These environmental factors affect how we spend each day and, as mounting evidence shows, how we age.

Since 1991, the University of Washington's Kame project has investigated the relationship between lifestyle and aging. Kame researchers, led by principal investigator Dr. Eric Larson and co-principal investigators Drs. Amy Borenstein Graves and Susan McCurry, have followed the aging of over 2000 older Japanese Americans living in Seattle and surrounding King County.

Funded by the National Institute on Aging, the Kame project was conceived as part of a cross-national study with collaborators in Hawaii and Japan. By comparing the same type of information collected from populations of ethnic Japanese living in different cultures, researchers sought to examine how rates of dementia differ among persons of Japanese heritage across the Pacific Rim, and to determine if lifestyle could affect risk for aging-related impairment in memory and function.

The Kame project started in 1990 with efforts to recruit as many eligible participants as possible. Census information indicated that about 3,000 people living in King County were eligible (over age 65 and of at least 50 percent Japanese heritage). Between May 1992 and May 1994, nearly 2,000 of those individuals enrolled in the project. Since that time, more than 200 additional participants have enrolled as they turned 65.

To ensure that subjects in Seattle, Hawaii, and Japan were assessed in comparable ways, a cognitive screening instrument was developed for use in cross-national studies. This test, called the Cognitive Abilities Screening Instrument (CASI), was administered to all Kame participants at the time they enrolled in the project and at regular follow-ups since 1994. Participants were also asked detailed questions to review their dietary, social and environmental background, and in some cases underwent additional neuropsychological testing and a thorough physical examination.

In the first two years of study enrollment, Kame researchers found that the prevalence of dementia among Japanese Americans in King County increased significantly with age. In the youngest age groups-65 to 74 years of age-the rate of dementia was less than 2 percent. In the older age groups-85 to 94 years of age-the rates of dementia were 30 to 50 percent. In the oldest age group-many of whom were over 95 years of age and living in residential care facilities -the rate of dementia was nearly 75 percent.

More than half of the cases of dementia were caused by Alzheimer's disease (AD). Dementia due to stroke accounted for about one quarter of the cases. Researchers found the types and rates of dementia among Japanese Americans in King County to be more similar to those found overall in the U.S. than to the types and rates found in Japan, where dementia is more often caused by stroke than by AD. Kame investigators are currently looking at whether rates of incident dementia (new cases) show this same pattern compared to cross-national studies, and investigating some of the genetic and environmental factors that may contribute to differing rates of cognitive decline.

Comparing results from the Kame project with studies of other populations, Kame researchers have found that environment may increase or decrease risk for cognitive decline, and also play a role in the development of AD. These results provide starting points for continuing research to determine how environmental factors might be changed to decrease AD and promote healthy aging.

For example, based on analysis of CASI results from a two-year follow up with Kame participants, researchers reported that the risk for cognitive decline was smaller for participants who continued a Japanese lifestyle, including diet and language, than for their counterparts whose lifestyle was less traditionally Japanese. Researchers suggest that this finding may be related to increased brain reserve-more connections among brain cells developed in response to stimulation from mental activities such as learning multiple languages.

In a study focused on brain reserve, Kame researchers found a relationship between AD and lower brain reserve, as measured by head circumference. Participants with AD who had smaller head circumferences and carried the ApoE-4 gene, which has been linked to increased risk for AD, had more severe memory problems than participants with AD who had larger head circumferences and did not carry this gene. This result is consistent with research suggesting that an increased risk of AD may be associated with environmental factors that affect brain growth and development early in life, during gestation and childhood.

The affect of estrogen is another environmental factor studied by Kame researchers. In a study of female Kame participants on post-menopausal hormone replacement therapy, researchers found that use of estrogen alone had a protective effect against cognitive decline. But when estrogen was combined with a second hormone, progestin, the protective effect disappeared.

These and other studies currently ongoing by Kame researchers have increased our understanding of the process of aging. Such research was made possible by the abundance of information provided by the Kame participants, who ranged in age from 65 to 108. The information provided by these individuals has enabled researchers to uncover relationships between lifestyle and the development of AD. Although much research remains to find ways prevent or slow the progress of AD, it is contributions like those made by the participants of the Kame project that pave the road of this long journey.

The Kame project will be ending next spring. Many Kame researchers will be involved in a national study of Gingko biloba to prevent decline and dementia. This four-year project, known as the GEM study, will begin by enrolling Seattle-area Kame participants who are eligible, and then other eligible participants from the general Asian American community. Participants must be at least 75 years of age in generally good health. For more information, contact Janice Enzmann at 206-326-2457.